Dynamic Inflammatory and Mood Predictors of Cognitive Aging in Bipolar Disorder

描述(申请人提供)：随着人口老龄化，由于严重的精神疾病，如双相情感障碍(BD)对认知和健康的影响，个人和社会的负担将增加。在许多健康和认知领域，BD的过早和加速衰老的轨迹已经开始被认识到，但具体的机制还没有确定，特别是在认知衰老的过程中。炎症功能的标记物，如细胞因子水平，已知会影响认知，随年龄变化，并预测精神健康的人的下降。细胞因子水平在BD患者中似乎也是异常的，但BD患者的情绪不稳定使测量炎症和认知指标的短期和长期变化具有挑战性。尽管如此，在这一人群中进行的研究提供了一个独特的机会，可以更好地理解情绪和行为失调程度的差异如何缓和或调节免疫-认知联系。我们建议使用创新的多队列突发纵向设计(MBLD)来表征认知和炎症反应的轨迹，并确定：1)短期内认知和炎症之间的关系，同时考虑情绪变异性的影响；2)炎症标记物中短期变异性的基线测量和水平，可能预测认知变化的长期轨迹；以及3)长期内炎症、认知和情绪变量之间的关系(即变化机制)。我们将评估144名成年人(35-60岁)和115名没有精神疾病的类似年龄的非BD对照(NC)参与者，这些人有双相情感障碍I诊断表明的与临床相关的情绪失调症状。认知、细胞因子水平和情绪(以及其他潜在的影响变量) 将使用密集的远程监测和家访(突发评估)在两周内每周或每天测量一次。BD组每年重复一次突发评估(纵向评估)，为期三年，NC组每年一次。该项目涉及NIMH战略目标2：绘制精神疾病轨迹图，以确定何时、何地和如何干预。具体地说，使用一种创新的设计，允许我们解释和测量情绪症状的可变性的影响，我们可以发现炎性标记物(静态和动态)，预测情绪不稳定个体的认知变化过程。通过了解炎症、认知和情绪之间复杂而动态的相互作用，可以设计药物和行为干预来减缓或扭转双相情感障碍功能下降的轨迹。

DESCRIPTION (provided by applicant): As the population ages, the burden on individuals and society due to the cognitive and health effects of serious mental illnesses, such as bipolar disorder (BD), will increase. Premature and accelerated aging trajectories in BD are beginning to be recognized in many health and cognitive domains, but specific mechanisms have not yet been identified, particularly for the course of cognitive aging. Markers of inflammatory function, such as cytokine levels, are known to affect cognition, change with age, and predict declines in mentally healthy individuals. Cytokine levels also appear to be abnormal in those with BD, but mood instability in BD makes measurement of short- and long-term changes in both inflammatory and cognitive measures challenging. Nonetheless, studies within this population afford a unique opportunity to better understand how variations in the degree of emotional and behavioral dysregulation may moderate or mediate immune-cognitive associations. We propose to use an innovative multi-cohort burst longitudinal design (MBLD) to characterize trajectories of cognitive and inflammatory response and identify: 1) relationships between cognition and inflammation in the short term while accounting for effects of mood variability, 2) baseline measures and levels of short-term variability in inflammatory markers that might predict long-term trajectories of cognitive change, and 3) relationships between inflammatory, cognitive, and mood variables in the long-term (i.e., mechanisms of change). We will assess 144 adults (35-60 years old) with clinically-relevant symptoms of mood dysregulation, as indicated by Bipolar I diagnosis, and 115 similarly aged non-BD comparison (NC) participants without mental illnesses. Cognition, cytokine levels, and mood (along with other potential contributing variables) will be measured weekly or daily over a two week period using intensive remote monitoring and home visits (burst assessment). Burst assessments will be repeated annually (longitudinal assessment) for three years in the BD group, and at one year in the NC group. This project addresses NIMH Strategic Objective # 2: charting mental illness trajectories to determine when, where, and how to intervene. Specifically, using an innovative design that allows us to account for, and measure the impact of, variability in mood symptoms, we can discover inflammatory markers (both static and dynamic) that predict the course of cognitive change among individuals with mood instability. By understanding the complex and dynamic interplay between inflammation, cognition, and mood, pharmacologic and behavioral interventions can be designed to slow or reverse the trajectory of declining function in bipolar disorder.